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The goal of this study was to demonstrate the functions and specific mechanism of long non-coding RNA (lncRNA) GNAS-AS1 in lung adenocarcinoma. Levels of lncRNA GNAS-AS1, microRNA (miR)-433-3p, and Rab3A were assessed by quantitative real-time PCR (qRT-PCR). The target-binding sites of lncRNA GNAS-AS1, miR-433-3p, and Rab3A were predicted and confirmed by bioinformatics tool (StarBase) and a dual-luciferase reporter system. Cell proliferation and apoptosis were checked using MTT and flow cytometry, respectively. Additionally, the levels of apoptosis-related and epithelial–mesenchymal transition (EMT)-associated genes in A549 cells were analyzed by qRT-PCR and western blot. We found that lncRNA GNAS-AS1 was upregulated, miR-433-3p was low-expressed, and Rab3A was overexpressed in lung adenocarcinoma tissues and cell lines. LncRNA GNAS-AS1 interacted with miR-433-3p and negatively regulated miR-433-3p levels. Rab3A was a direct target of miR-433-3p. Downregulation of lncRNA GNAS-AS1 remarkably suppressed cell proliferation, promoted cell apoptosis, decreased B-cell lymphoma-2 (Bcl-2) expression, enhanced the Bcl-2-Associated X (Bax) level, promoted E-cadherin expression, and reduced N-cadherin and Rab3A levels. However, the miR-433-3p inhibitor reversed all these findings. Similarly, the inhibitory effects of miR-433-3p mimic on A549 cells were reversed by the Rab3A-plasmid. In conclusion, lncRNA GNAS-AS1 downregulation suppressed lung adenocarcinoma cell proliferation and EMT through the miR-433-3p/Rab3A axis.

Hydrogenation of biomass-derived levulinic acid (LA) could produce a high value-added compound, gamma-valerolactone (GVL). However, metal leaching is a major issue in the efficient production of GVL from LA due to the acidity of LA. Some endeavors have tended to focus on the external factors of the catalysts for preventing metal leaching, such as reaction at high temperature and H2 pressure or the esterification of LA with alcohols. Focusing on the catalyst itself, in this work, metal leaching was overcome by the selection of suitable catalyst compositions and preparation methods. The CuAgZrGO catalyst was synthesized by regulating the pH of the precipitation system to achieve a one-pot layered assembly of Zr4+, Cu2+, and Ag+ components on the graphene oxide (GO) surface at the atomic level. The catalyst without reduction pretreatment resulted in the complete conversion of LA and achieved approximately 100% yield of GVL, and metal leaching in the LA aqueous phase could be substantially prevented. Under mild reaction conditions, the catalyst exhibited good stability after four times of recycling in the aqueous phase. The positive-titration co-precipitation method controls the Ag more scattered on the surface of Cu and Zr precipitates, which makes CuAgZrGO a metal-leaching-resistant catalyst for aqueous-phase hydrogenation of LA. [ABSTRACT FROM AUTHOR]

Background and Aims: Sleep is predicted as a key modulator of cognition, but the underlying mechanisms are poorly understood. In this study, we investigated the effects of melatonin on chronic rapid eye movement sleep deprivation (CRSD)‐induced cognitive impairment and circadian dysfunction in rat models. Methods: Thirty‐six Sprague‐Dawley male rats were divided into three groups: CRSD with saline treatment, CRSD with chronic melatonin injection (20 mg/kg/day), and non‐sleep‐deprived control. The cognitive behavioral tests as well as the expression of clocks and HDAC3 were evaluated in all groups. Results: CRSD significantly reduced recognition index in novel object location, increased escape latency and distance traveling in Morris water maze while melatonin treatment attenuated CRSD‐induced hippocampal‐dependent spatial learning and memory deficits. Furthermore, the mRNAs of brain and muscle aryl hydrocarbon receptor nuclear translocator‐like 1(Bmal1) and circadian locomotor output cycles kaput (Clock) were globally down‐regulated by CRSD with constant intrinsic oscillation in both hippocampus and peripheral blood. The protein levels of hippocampal Bmal1, Clock, and HDAC3 were also remarkably down‐regulated following CRSD. Melatonin treatment reversed CRSD‐induced alterations of Bmal1/Clock and HDAC3 on both mRNA levels and protein levels. Conclusions: Our data indicate that melatonin treatment attenuates CRSD‐induced cognitive impairment via regulating HDAC3‐Bmal1/Clock interaction. These findings explore a broader understanding of the relationship between sleep and cognition and provide a potential new therapeutic target for cognitive impairment. [ABSTRACT FROM AUTHOR]

Objective: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving both upper and lower motor neurons. The motor phenotypes of ALS are highly clinically heterogeneous, and the underlying mechanisms are poorly understood. Methods: A comparative proteomic analysis was performed in the cerebrospinal fluid (CSF) of bulbar‐onset (BO) and spinal‐onset (SO) ALS patients and controls (n = 14). Five biomarker candidates were selected from a differentially regulated protein pool, and further validation was performed in a larger independent cohort (n = 92) using enzyme‐linked immunosorbent assay (ELISA). Results: A total of 1732 CSF proteins were identified, and 78 differentially expressed proteins were found among BO‐ALS patients, SO‐ALS patients, and controls. Five promising biomarker candidates were selected for further validation, and lipopolysaccharide‐binding protein (LBP) and HLA class II histocompatibility antigen, DR alpha chain (HLA‐DRA) were validated. CSF LBP levels were increased in ALS patients compared with controls and higher in BO‐ALS versus SO‐ALS. The increased CSF LBP levels were correlated with the revised ALS Functional Scale (ALSFRS‐R) score. CSF HLA‐DRA levels were specifically elevated in BO‐ALS patients, and there was no significant difference between SO‐ALS patients and controls. Increased HLA‐DRA expression was correlated with decreased survival. Interpretation: Our data shows that elevated CSF LBP is a good biomarker for ALS and correlates with clinical severity, and increased HLA‐DRA is a specific biomarker for BO‐ALS and may predict short survival. It also suggests that the microglial pathway and HLA‐II‐related adaptive immunity may be differentially involved in ALS phenotypes and may be new therapeutic targets for ALS. [ABSTRACT FROM AUTHOR]

In order to increase molecular weight of PLGA, BuOH was introduced as a co-initiator to Sn[(Oct).sub.2] in ring-opening precipitation polymerization of L-lactide and glycolide in supercritical carbon dioxide (Sc[CO.sub.2]). The polymerization mechanism of the reaction processes on Sn[(Oct).sub.2] with BuOH was explored. The positive effect of BuOH on polymer molecular weight was studied. PLGA with higher [M.sub.w] (of 19,500 g/mol) and narrower PDI (of 1.12) was successfully prepared by ring-opening precipitation polymerization in ScC02 using Sn[(Oct).sub.2]/BuOH as an efficient catalytic system.Influence of reaction conditions, such as monomer feed concentration, reaction temperature, pressure, and time, were also investigated in detail. POLYM. ENG. SCI., 54:704-710, 2014. © 2013 Society of Plastics Engineers, INTRODUCTION Poly (L-lactide-co-glycolide) (PLGA), due to its advantages of biocompatibility, degradability, processability, and mechanical strength, has been widely used for medical applications including the controlled release of drugs, absorbable sutures, [...]